Pneumocystis Pneumonia

Pneumocystis pneumonia is a severe, often life threatening pneumonia caused by the fungus Pneumocystis jirovecii. It occurs predominantly in immunocompromised hosts, most classically in advanced HIV infection with a low CD4 count. It is increasingly recognised in non HIV immunocompromised populations, including transplant recipients and patients on prolonged corticosteroid or other immunosuppressive therapy, where the disease course is often more rapidly progressive and severe.

Pathophysiology and risk stratification

The organism, an atypical fungus with biological features overlapping both fungi and protozoa, colonises the alveolar spaces and triggers an intense host inflammatory response that itself contributes significantly to the resulting lung injury and hypoxia.

In HIV infection, risk rises sharply below a CD4 count of 200 cells per microlitre, forming the basis for prophylaxis thresholds.

In non HIV immunosuppression, prolonged corticosteroid therapy (typically prednisolone equivalent of 20 mg daily or more for four weeks or longer) is a major recognised risk factor.

A subacute onset over days to weeks of progressive breathlessness, dry non productive cough and low grade fever is characteristic, notably more insidious in HIV associated disease compared with the typically more rapid, fulminant onset seen in non HIV immunocompromised patients.

Examination is frequently unremarkable relative to the severity of hypoxia and radiographic changes, a characteristic and important clinical discordance, with exertional desaturation (a fall in oxygen saturation on walking or exertion, even with a normal resting saturation) a useful and sensitive clinical sign.

Progressive hypoxia, tachypnoea and, in severe cases, respiratory failure requiring ventilatory support develop as the illness progresses if untreated.

Chest radiography classically shows bilateral, diffuse, perihilar interstitial infiltrates, though can be normal early in the illness, with high resolution computed tomography showing characteristic bilateral ground glass opacification with greater sensitivity for earlier or milder disease.

Microbiological confirmation is obtained from induced sputum or, with greater sensitivity, bronchoalveolar lavage fluid, using immunofluorescence staining or polymerase chain reaction to identify the organism, since it cannot be cultured using standard techniques.

Serum beta D glucan, a fungal cell wall component, is elevated in the majority of cases and, while non specific for this organism alone, is a useful supportive test, particularly where bronchoscopy is not immediately feasible.

Arterial blood gas analysis quantifies the degree of hypoxia and guides both severity assessment and the decision to add adjunctive corticosteroid therapy, and HIV testing should be performed in any patient presenting with this infection without a known predisposing cause.

High dose co trimoxazole (trimethoprim with sulfamethoxazole) is first line treatment. Dose 15 to 20 mg per kg per day of the trimethoprim component, divided into three or four doses, for a total duration of 21 days. Give it intravenously for severe disease or orally for milder presentations.

Adjunctive corticosteroid therapy is indicated where the arterial oxygen tension on room air is below 70 mmHg or the alveolar arterial oxygen gradient exceeds 35 mmHg. Use prednisolone 40 mg twice daily for five days, then 40 mg once daily for five days, then 20 mg once daily for the remainder of the treatment course. Start ideally within 72 hours of antimicrobial treatment initiation, given evidence of mortality benefit in moderate to severe disease.

Alternative treatments for patients unable to tolerate co trimoxazole (sulfa allergy, significant adverse effects) include intravenous pentamidine, or oral combinations of clindamycin with primaquine or dapsone with trimethoprim. Select according to disease severity and specific contraindications. Desensitisation to co trimoxazole is considered in some cases given its superior efficacy.

Prophylaxis is indicated for HIV positive patients with a CD4 count below 200 cells per microlitre. Use co trimoxazole 480 mg (or the double strength 960 mg tablet three times weekly as an alternative regimen) once daily. It is continued until the CD4 count has risen above 200 cells per microlitre on antiretroviral therapy for at least three months.

Prophylaxis is also indicated for non HIV immunocompromised patients meeting risk thresholds (prolonged high dose corticosteroid therapy, certain haematological malignancies, transplant recipients).

Dapsone, atovaquone or nebulised pentamidine are alternatives in co trimoxazole intolerant patients.

Initiation of antiretroviral therapy in HIV associated disease is generally recommended within two weeks of starting pneumocystis treatment, balancing the benefit of earlier immune reconstitution against the risk of immune reconstitution inflammatory syndrome, under specialist HIV guidance.